Chemical shift assignments of the catalytic domain of Staphylococcus aureus LytM (original) (raw)

2023, Biomolecular NMR Assignments

Nigo et al. 2017). To treat (multi)resistant bacterial infections new cures are urgently needed. Lysins represent a novel group of potential antibacterial agents with a new mechanism of action. Lysins are naturally occurring bacterial cell wall hydrolyzing enzymes (peptidoglycan hydrolases, PGHs), which when engaged in therapeutics induce bacteriolysis (Schuch et al. 2022). PGHs are classified according to the specific type of bond they cleave. PG endopeptidases hydrolyze bonds within the peptidic moieties in the bacterial PG, which in S. aureus consist of two stem peptides (Ala-D-iso-Gln-Lys-D-Ala) crosslinked by pentaglycine cross-bridges. The latter is the target of the glycyl-glycine endopeptidase LytM, one of S. aureus autolysins (Ramadurai et al. 1999). We have recently assigned the chemical shifts of the LytM N-terminal domain and the linker region, encompassing residues 26-184, for the characterization of its structure and interactions (Pitkänen et al. 2023). LytM catalytic domain (LytM CAT, residues 185-316), is structurally homologous to lysostaphin and other MEROPS M23B family of metallo-endopeptidase catalytic domains (Firczuk et al. 2005; Grabowska et al. 2015). These enzymes have in common a characteristic narrow groove formed by a β-sheet and four surrounding loops. At one end of the groove, a Biological context Staphylococcus aureus is a pathogen of great concern because of its ability to cause life-threatening infections and its increasing resistance to antibiotics. Methicillin-resistant S. aureus, MRSA, causes infections hard to treat, but strikingly, MRSA strains with concomitant resistance to many other commonly used groups of antibiotics have emerged. Most alarmingly, MRSA resistance to vancomycin, linezolid, ceftaroline and daptomycin, the last-resort drugs approved for the treatment of MRSA, has been reported